Back to the history of medicine

There are a few angles that have me thinking back to the history of medication and the sort of lessons that might be drawn from it.

Drug discovery

I've mentioned before that what science has looked like throughout history often differs from many in the scientific community seem to think is has. Major journals like The Lancet and Nature only started sending out papers for external peer review in the 1970s for example. The same seems to apply to how some critical drugs were developed:

Fighting pandemics with mandatory masks

One problem noted there - and you might expect with current measures - are questions of just how long the public is likely to be willing to tolerate them.


You may not have heard much about this but it's the precursor to modern vaccinations. It involved deliberately infecting people with a small dose of smallpox in order to significantly improve survivability from the infection. I'd heard of this before, but in the covid19 context it was Robin Hanson that seems one of its early vocal advocates as a possible way to address the current pandemic.

The medical literature consistently finds strong relations, in both animals and humans, between initial virus dose and symptom severity, including death. The most directly relevant data is on SARS and measles, where natural differences in doses were associated with factors of 3 and 14 in death rates, and in smallpox, where in the 1700s low “variolation” doses given on purpose cut death rates by a factor of 10 to 30. For example, variolation saved George Washington’s troops at Valley Forge.

He notes that using lockdowns to try to prevent of a disease may have the effect of increasing the fatality rate from the a disease like the one behind the current pandemic, as being trapped in close confinement could cause an initially infected person spreading the infection to those they live with by in higher (and thus more dangerous) initial doses.

Now I see Scott Gottlieb talking of viral load, pointing to an New York Times article. The author of that article spends much of it talking about the risk which is certainly a legitimate concern. He says this:

It would be unethical to experimentally manipulate viral dose in humans for a pathogen as serious as the coronavirus, but there is evidence that dose also matters for the human coronavirus. During the 2003 SARS coronavirus outbreak in Hong Kong, for instance, one patient infected many others living in the same complex of apartment buildings, resulting in 19 dead.

I keep finding myself thinking to what extent I should buy the arguments of the current medical ethicists though. At the moment it seems that one major reason why the US has failed to respond well to the current pandemic seems to have been concerns by the CDC and the FDA over ethics and safety regulations1.

Here I think Hanson's words are useful - I suggest reading the whole post. It's worth knowing thatthere's not yet adequate data to answer some questions and testing which does legitimately pose a risk would be needed to address them. Controlled infection is one strange way to go about actually "flattening the curve", could help move society closer to herd immunity, and could have savings in lives that might overwhelm any lost.

Of course, if low doses cut death rates by a factor of two or more, variolation volunteers would actually cut their chance of death, perhaps greatly. Yes, the first few thousand volunteers could be less sure of such gains, but they could be compensated for this risk, just as we now consider compensating subjects in vaccine trials using live Covid19 viruses. We could pay variolation volunteers cash, offer their loved ones priority medical care, certify them as safe for work and social gatherings, and honor them like soldiers selected for their elite features who take risks to produce community gains.

It seems to me that often people look at risk as something you either take or you don't rather than looking enough at offsetting one type of risk against another.

  1. It also seems worth asking the question as to whether or not caution by regulators is a cause of a significant slowdown in the development of new drugs ↩︎

More moves towards masks

Interestingly, since the last post here it seems that both the CDC and US Surgeon General have doubled down on advice to avoid use of face masks. Still suspecting that that advice may be changing soon regardless, given other moves. Here's another tweak from Scott Gottlieb the former FDA commissioner for example:

One reason that I've concentrated on him is that he seems to be one of the few both having a history of being critical of the Trump administration's response while, particularly lately, still being respected by those in the administration. Encouraging the public to wear masks is also a component of the report he's put together showing how to reopen society. Speaking to Good Morning America, Dr. Fauci - a face you're likely to see in Trump press conferences - also seems to find some support for the position.

At the moment, looking at the still emerging research, it seems as though the Czech Republic - the first country in Europe to have required wearing masks in public - seems to have successfully flattened the curve. Just within the last day or so the Germany Health Ministry is starting to echo the advice of the German Medical Association to wear masks, Austria has mandated wearing masks in supermarkets and Bulgaria has made wearing masks in public places compulsory.

The Czech Prime Minster has been publicly calling for Trump to require masking in public and it seems to me that there are actually quite politically compelling reasons for Trump to do so. In general in politics one need not tell a true story - it only needs to be true enough to be able to sell it to the public. If you look at how the CDC and the FDA obstructing testing are key reasons as to why the US is in the poor position it currently is, it becomes easier to sell a (generally false) narrative of Trump bravely fighting the Deep State. It doesn't matter that the Surgeon General has attempted to suck to Trump in very cringey and false ways - I look at Trump as a narcissistic sociopath who has no loyalty to anyone other than himself. If he can act in ways which seem to be ahead of organizations like the CDC and the WHO1 in adopting policies that are later more generally accepted (and for which a decent base of evidence appears to continue to be building) that seems to provide a fair bit of cover for his prior (and continuing) incompetence.

  1. Interestingly, the Chief Scientist of the World Health Organization tweeting "in personal capacity" has also retweeted an interview in in Science Magazine with the head of the Chinese CDC with the headline Not wearing masks to protect against coronavirus is a ‘big mistake,’ top Chinese scientist says↩︎

At what point is the only responsible course of action to disband the WHO?

Every time I hear something new about the World Health Organization it seems to just get worse and worse and worse. I'm beginning to think that the only responsible course of action at this point is to shut it down as a public health threat.

It no doubt has a lot of competent people working but it but it's errors and omissions seem at this point entirely inexcusable. Just one of today's additions to the WHO backstory is discovering that back in 2017 the New York Times reported claims and evidence that the man now in charge of the WHO had been responsible for covering up evidence of cholera epidemics as health minister of Ethiopia. And there's there this segment of an interview with RTHK in Hong Kong:

Bruce Aylward was described in February by the CBC as team lead on the WHO-China joint mission on COVID-19. Why is Taiwan of particular relevance here? They warned the WHO of human-to-human transmission in late December ... and the WHO didn't pass the information along:

The timing of that puts it a day after Li Wenliang in Wuhan sent out a warning that authorities in China tried to suppress - i.e. the timing of Taiwan's warning fits the data. The World Health Organization, by contrast, stated two weeks later that preliminary investigations found little evidence of human-to-human transmission.

Then there was the issue of travel bans - again something advised against by the WHO back in January. Now that it at least claims to have gotten things under control in the country - though its claim seems suspicious - even China is banning almost all foreigners from traveling into the country.

Then there's the issue of wet markets where the latest virus seems to have originated - as did the previous SARS virus. Is the WHO calling for those to be shut down and replaced with something more sanitary? Nope. Instead they're merely offering tips for working there1.

And then it comes to the issues of masks, this is what a WHO account still was saying on March 26:

That's not the same tone you'll see if you compare to certain other parts of the world, and it seems that by and large those parts of the world that have adopted universal mask-wearing have had better success dealing with the current problems.

The New York Times article cites a study finding that for the previous SARS virus mask-wearing as an intervention appeared to be more effective protection than washing your hands 10 times a day - though you certainly can (and probably should) do both.

It seems to me that the WHO's guidance re: masks (which is still both the official approach taken by both the CDC and the corresponding government agency in the country where I'm living) is - as described on the British Medical Journal's blog - "confusing".

There don't seem to be enough masks to go around, so you could also that one should safe available masks for those in the healthcare sector and then give secondary priority to those in jobs requiring contact with a lot of different people but that's not generally the argument being made. A previous New York Times article suggesting that this seemed to make authorities appear untrustworthy which might actually fuel hoarding of surgical and N95 masks.

Instead a better idea might be to encourage improvised masks. The Czech Republic has made masks mandatory in public and improvisation wherein people frequently sow their own masks seems to be the course that country has staten. The German Medical Association is also now advising people to wear makeshift masks at all times.

If governments start encouraging mask-wearing then they can also start to point people to ways to make more effective improvised masks. The South China Morning Post has published instructions on how to make masks that performed 80-90% as effectively as surgical masks in testing, for example, and other research exists as to the effectiveness of different materials you could use for homemade mask-making. (Based on additional research it also appears that it's possible to render N95 masks sanitary for reuse without loss of filtering ability but those masks remain harder to come by).

If the mask shortage can be addressed by adoption of improvised masks it may then prove possible to adopt the suggestion found in the article Rational use of face masks in the COVID-19 pandemic which was published a days back in The Lancet Respiratory Medicine:

Perhaps it would also be rational to recommend that people in quarantine wear face masks if they need to leave home for any reason, to prevent potential asymptomatic or presymptomatic transmission. In addition, vulnerable populations, such as older adults and those with underlying medical conditions, should wear face masks if available. Universal use of face masks could be considered if supplies permit.

To move to a point wherein mask-wearing becomes universal again goes against the WHO's recommendations. I'm hoping that the US begins to move towards a change in it's official advice - this Twitter-verified account says that a change in the CDC recommendation on mask wearing will happen within the next ten days. I'd like to see a better source for this but with the 2017-2019 head of the FDA tweeting like this back on March 18th and then saying this on video on a Wall Street Journal twitter account on March 25th I certainly wouldn't be shocked by such a change in advice. Former President Obama also tweeted a link to an article wherein mask-wearing was one of the suggestions made.

Thinking back through all the above, I see the WHO as an organization now headed by a man with a history of covering up epidemics and who seemed to be attempting to cover another up in January. It was that same organization that refused to disseminate the information previously received from Taiwan about human-to-human transmission and has shown itself to be childish in its attempts to avoid discussing Taiwan. Its advice in general in these circumstances appears to have been quite poor in general2 and in some ways possibly even counterproductive.

At what point are the only reasonable courses of action to either disband the WHO entirely, or instead to revoke the membership of the People's Republic of China and grant membership to the Republic of China (i.e. Taiwan) instead? I keep finding myself thinking back to the League of Nations formed following the First World War with the intention of stopping further such conflicts. It failed and then in the wake of the Second World War the United Nations - of which the World Health Organization is a member agency - was formed. What should you do when prominent international organizations seems highly ineffective?

  1. One reason that I don't want to target criticism too heavily on wet markets is that factory farming is another danger area↩︎

  2. I haven't even discussed here the problems in the data distributed by the World Health Organization. You'll find, for example, on Our World In Data, a section of the coronavirus information page entitled "Why we stopped relying on data from the World Health Organization" - they instead use data from the European CDC these days. ↩︎

Random links

Mystery deepens over ex-Interpol chief Meng
Looking at how the WHO has been behaving in China recently, I kept thinking to how they disappeared the then-head of Interpol in country about a year and a half ago. Eventually showed up in government custody and supposedly confessed to corruption charges, though given the country in question I wonder what happened behind the scenes.
Conservative faculty appear to influence their students more than liberal professors do
"When we break that down by political leaning, about the same proportion of students — 29 to 30 percent — say they became more liberal in college, whether or not they felt any pressure from faculty members. By contrast, among students who said they felt political pressure from conservative faculty members “frequently” or “all the time,” a slightly larger proportion did become conservative, compared with those who felt less pressure."
The richest families in Florence in 1427 are still the richest families in Florence\
"these families were able to maintain their wealth through various sieges of Florence, Napoleon’s campaign in Italy, Benito Mussolini’s dictatorship, and two world wars." Less uncommon than you might expect I think.
Dry-Brining Is the Best Way to Brine Meat, Poultry, and More
I do enjoy ways of simplifying cooking without seemingly much - if any - of a negative impact on flavour. "Ah, some people may say here. But if you flavor your brine with delicious things like fruit juices, stock, herbs, spices, sugar, and more, then surely your meat will be more delicious than if you just soaked it in a plain old salt-water solution. Sorry, but nope! As Kenji has shown before in his article on turkey brining, flavor molecules, unlike salt, are for the most part too big to penetrate the cell membranes of a piece of meat; your brine may taste flavorful, but your roast will not." (also discusses issues re: dilution of flavour and difficulty browning)


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